Exploring the Efficacy of the Paula Method of Muscle Exercises in Managing Low Anterior Resection Syndrome Using an Integrative Approach: A Preliminary Study.

Background: Low anterior resection syndrome (LARS) is a post-proctectomy consequence characterized by variable and unpredictable bowel function, including clustering, urgency, and incontinence, which significantly impacts the quality of life. Currently, there is no established gold-standard therapy for LARS. Primary Study Objective: This study aimed to evaluate the effectiveness of the Paula method of exercise as part of an integrative treatment approach for patients with LARS. Design: This preliminary study utilized a single-arm pretest-posttest design. Setting: The study was conducted at a tertiary care medical center. Participants: Five patients diagnosed with LARS completed the study. Intervention: Participants underwent twelve weeks of individualized Paula method exercise sessions. Two questionnaires were employed to assess the severity of LARS and quality of life. Primary Outcome Measures: (1) Low Anterior Resection Syndrome (LARS) Score; (2) Memorial Sloan Kettering Cancer Bowel Function Instrument (MSK-BFI); (3) Global Quality-of-Life (QOLS) Score . Results: All participants completing the 12-week Paula exercise regimen reported no difficulty in engaging with the exercises. Statistically significant improvements were observed in both the LARS score and MSK-BFI (P = .039 and P = .043, respectively, Wilcoxon Rank Sum test). While there were improvements in the global quality-of-life score and functional scales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, these improvements did not reach statistical significance. Conclusions: This preliminary study suggests that patients with LARS can successfully complete a 12-week exercise program using the Paula method, resulting in improved LARS scores. However, further investigation through larger, multicenter, randomized controlled trials is necessary to establish the efficacy of these exercises as a treatment for LARS.

Incidence and Risk Factors for Low Anterior Resection Syndrome following Trans-Anal Total Mesorectal Excision.

BACKGROUND: Trans-anal total mesorectal excision (Ta-TME) is a novel approach for the resection of rectal cancer. Low anterior resection syndrome (LARS) is a frequent functional disorder that might follow restorative proctectomy. Data regarding bowel function after Ta-TME are scarce. The aim of this study was to evaluate the incidence and risk factors for the development of LARS following Ta-TME. METHODS: A prospectively maintained database of all patients who underwent Ta-TME for rectal cancer at our institution was reviewed. All patients who were operated on from January 2018 to December 2021 were evaluated. The LARS score questionnaire was used via telephone interviews. Incidence, severity and risk factors for LARS were evaluated. RESULTS: Eighty-five patients underwent Ta-TME for rectal cancer between January 2018 and December 2021. Thirty-five patients were excluded due to ostomy status, death, local disease recurrence, ileal pouch or lack of compliance. Fifty patients were included in the analysis. LARS was diagnosed in 76% of patients. Anastomosis distance from dentate line was identified as a risk factor for LARS via multivariate analysis (p = 0.042). Neo-adjuvant therapy, hand sewn anastomosis and anastomotic leak did not increase the risk of LARS. CONCLUSION: LARS is a frequent condition following ta-TME, as it is used for other approaches to low anterior resection. Anastomosis distance from dentate line is an independent risk factor for LARS. In this study neo-adjuvant therapy, hand sewn anastomosis and anastomotic leak did not increase the risk of LARS. Further studies with longer follow-up times are required to better understand the functional outcomes following Ta-TME.

A patient tailored approach to the surgical treatment of hemorrhoids leads to equal satisfaction following hemorrhoidectomy, stapled hemorrhoidopexy or a combination of both.

PURPOSE: Up to 20% of patients suffering from symptomatic hemorrhoids will require surgery. Excisional hemorrhoidectomy (EH) and stapled hemorrhoidopexy (SH) are both standard and safe procedures. While SH has a short-term advantage of faster recovery and lower postoperative pain, its long-term efficacy is debatable. This study aims to compare the outcomes of EH, SH, and a combined procedure of both. METHODS: A retrospective study compared the outcomes of patients treated surgically for hemorrhoids over a 5-year period. Eligible patients were asked by phone to complete a questionnaire evaluating recurrent symptoms, fecal incontinence, satisfaction, and self-assessed improvement in quality of life (QOL). RESULTS: This study included 362 patients, of whom 215 underwent SH, 99 underwent EH, and 48 underwent a combined procedure. No statistically significant differences were found between groups regarding complications, symptoms recurrence, or fecal incontinence. Combined procedure patients had significantly higher self-assessed improvement in QOL (P=0.04). CONCLUSION: In patients with symptomatic hemorrhoids, a tailored approach to symptomatic hemorrhoids is associated with high satisfaction rates and self-assessed improvement in QOL.

Urinary dysfunction in women following total mesorectal excision versus partial mesorectal excision for treatment of rectal cancer.

BACKGROUND: Colorectal cancer is a condition which is associated with substantial morbidity and mortality. The aim of this study was to assess urinary dysfunction and its effect on quality of life in women who underwent total mesorectal excision compared to women treated by partial mesorectal excision for treatment of rectal cancer. METHODS: We performed a retrospective cohort study at a tertiary university hospital between January 2014 and December 2019. A comparison was performed between women who underwent total mesorectal excision as opposed to partial mesorectal excision for treatment of rectal cancer. Pre-operative, intra-operative and post-operative data were compared between groups. Data regarding radiation therapy was recorded and compared as well. Urinary dysfunction and its impact on quality of life were assessed using UDI-6 and USIQ questionnaires. Further univariate and multivariate analyses were performed in the attempt of assessing risk factors for urinary dysfunction. RESULTS: A total of 107 women were included in the study, 73 women underwent partial mesorectal excision as opposed to 34 women who were treated by total mesorectal excision. Twenty-five women in the TME group underwent radiation therapy prior to surgery as opposed to none in the PME group (p < 0.001). Urinary dysfunction following surgery as assessed using the UDI-6 questionnaire did not differ between groups. Similar findings were recorded with regard to the impact of urinary dysfunction on quality of life as assessed using the USIQ questionnaire. Following multivariate analysis longer hospital stay was associated with increased risk of some degree of urinary dysfunction. CONCLUSIONS: Women undergoing total mesorectal excision have comparable results to partial mesorectal excision with regard to urinary dysfunction.

In and out: an analysis of epibiotic vs periplasmic bacterial predators.

Bdellovibrio and like organisms (BALO) are obligate predators of Gram-negative bacteria, belonging to the α- and δ-proteobacteria. BALO prey using either a periplasmic or an epibiotic predatory strategy, but the genetic background underlying these phenotypes is not known. Here we compare the epibiotic Bdellovibrio exovorus and Micavibrio aeruginosavorus to the periplasmic B. bacteriovorus and Bacteriovorax marinus. Electron microscopy showed that M. aeruginosavorus, but not B. exovorus, can attach to prey cells in a non-polar manner through its longitudinal side. Both these predators were resistant to a surprisingly high number of antibiotic compounds, possibly via 26 and 19 antibiotic-resistance genes, respectively, most of them encoding efflux pumps. Comparative genomic analysis of all the BALOs revealed that epibiotic predators have a much smaller genome (ca. 2.5 Mbp) than the periplasmic predators (ca. 3.5 Mbp). Additionally, periplasmic predators have, on average, 888 more proteins, at least 60% more peptidases, and one more rRNA operon. Fifteen and 219 protein families were specific to the epibiotic and the periplasmic predators, respectively, the latter clearly forming the core of the periplasmic 'predatome', which is upregulated during the growth phase. Metabolic deficiencies of epibiotic genomes include the synthesis of inosine, riboflavin, vitamin B6 and the siderophore aerobactin. The phylogeny of the epibiotic predators suggests that they evolved by convergent evolution, with M. aeruginosavorus originating from a non-predatory ancestor while B. exovorus evolved from periplasmic predators by gene loss.

Self-Protective mechanism awakened by glutamate in retinal ganglion cells.

The progression of degeneration in chronic optic neuropathies or in animal models of optic nerve injury is thought to be caused, at least in part, by an increase in glutamate to abnormally high concentrations. We show here that glutamate, when injected in subtoxic amounts into the vitreal body of the rat eye, transduces a self-protecting signal that renders the retinal ganglion cells resistant to further toxicity, whether glutamate-derived or not. This neuroprotective effect is attained within 24 h and lasts at least 4 days. Western blot analysis of rat retinas revealed increased amounts of bcl-2 four days after injection of glutamate in either subtoxic or toxic (120 nmol) amounts, but not after saline injection. The effects of intravitreal glutamate or saline injection on the secretion of neurotrophins by retinal ganglion cells was evaluated in rat aqueous humor 6 h, 1 day, and 4 days after injection. Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 showed similar kinetic patterns in all of the eyes; that is, they increased to a peak 1 day after the injection and returned to normal by day 4. However, increased amounts the neurotrophin receptor TrkA within the retinal ganglion cell layer and nerve fiber layer were detected 1 day after injection of glutamate in either toxic or subtoxic amounts, but not after saline injection. This finding points to the possible involvement of neurotrophin receptors in regulation of the cellular responses to glutamate challenge. Identification of the intracellular signals that trigger the glutamate-induced self-protective mechanism would shed light on the genetic balance needed for survival, and guide the development of drugs for the up-regulation of desired genes and their products.

Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity.

Neurotrophins (NTs) promote neuronal survival and maintenance during development and after injury. However, their role in the communication between the nervous system and the immune system is not yet clear. We observed recently that passively transferred activated T cells of various antigen specificities home to the injured central nervous system (CNS), yet only autoimmune T cells specific to a CNS antigen, myelin basic protein (MBP), protect neurons from secondary degeneration after crush injury of the rat optic nerve. Here we examined the involvement of NTs in T-cell-mediated neuroprotection, and the possible significance of the antigen specificity of the T cells in this activity. Analysis of cytokine and NT expression in various rat T cell lines showed that the T cells express mRNA for cytokines of Th1, Th2, and Th3 phenotypes. In addition, the T cells express mRNA and protein specific to nerve growth factor, brain-derived neurotrophic factor, NT-3, and NT-4/5. Antigen activation significantly increased NT secretion. Thus, reactivation of CNS autoimmune T cells by locally presented antigens to which they are specific can lead to enhanced secretion of NTs and possibly also of other factors in injured optic nerves. mRNA for TrkA, TrkB and p75 receptors was expressed in the injured nerve, suggesting that these specific receptors can mediate the effects of the T-cell-derived NTs. The neuroprotective effect of the passively transferred autoimmune anti-MBP T cells in injured optic nerves was significantly decreased after local applicaiton of a tyrosine kinase inhibitor known to be associated with NT-receptor activity. These results suggest that the neuroprotective effect of autoimmune T cells involves the secretion of factors such as NTs by the T cells reactivated by their specific antigen in the injured CNS. T cell intervention in the injured CNS might prove to be a useful means of promoting post-injury CNS maintenance and recovery, possibly via supply of NTs and other factors.

Exertional heat stroke--the prevention of a medical emergency.

In most cases, exertional heat stroke (EHS) can be prevented in the military setting. The actions taken by the Israel Defense Forces (IDF) and their outcome prove this well. Unfortunately, despite the available information, there are still incidents of failure of command in conducting physical exercise, leading to EHS. In our experience, most incidences are a consequence of disregarding safety regulations. The application of simple and reasonable measures will not only prevent accidents from happening, but will also result in better trained soldiers.

Differential T cell response in central and peripheral nerve injury: connection with immune privilege.

The central nervous system (CNS), unlike the peripheral nervous system (PNS), is an immune-privileged site in which local immune responses are restricted. Whereas immune privilege in the intact CNS has been studied intensively, little is known about its effects after trauma. In this study, we examined the influence of CNS immune privilege on T cell response to central nerve injury. Immunocytochemistry revealed a significantly greater accumulation of endogenous T cells in the injured rat sciatic nerve than in the injured rat optic nerve (representing PNS and CNS white matter trauma, respectively). Use of the in situ terminal deoxytransferase-catalyzed DNA nick end labeling (TUNEL) procedure revealed extensive death of accumulating T cells in injured CNS nerves as well as in CNS nerves of rats with acute experimental autoimmune encephalomyelitis, but not in injured PNS nerves. Although Fas ligand (FasL) protein was expressed in white matter tissue of both systems, it was more pronounced in the CNS. Expression of major histocompatibility complex (MHC) class II antigens was found to be constitutive in the PNS, but in the CNS was induced only after injury. Our findings suggest that the T cell response to central nerve injury is restricted by the reduced expression of MHC class II antigens, the pronounced FasL expression, and the elimination of infiltrating lymphocytes through cell death.

Near-field optical photomask repair with a femtosecond laser.

We present a high-resolution near-field optical tool designed for repair of opaque defects in binary photomasks. Both instrument design and near-field imaging and patterning results will be presented. Designed for ablative processing of thin metal films, the MR-100 incorporates an industrial amplified femtosecond laser, third harmonic generator and built-in autocorrelator. The ultrashort duration of the femtosecond pulses enables the tool to remove chrome layers with negligible damage to the surrounding metal or the underlying quartz substrate. The micropipette based near-field writing head can deliver power densities of hundreds of GW/cm2 to spots of several hundred nanometres and below. Repairs on sample masks will be presented and the repair quality will be discussed.

Nanostructuring with spatially localized femtosecond laser pulses.

Spatially localized femtosecond pulses have been produced by a combination of scanning near-field optical microscopy with ultrashort pulse lasers. With these pulses direct ablative writing on metal surfaces is demonstrated. Possible applications of this technique for nanostructuring, repair, and production of lithographic masks are discussed.

GTP-dependent conformational changes associated with the functional switch between Galpha and cross-linking activities in brain-derived tissue transglutaminase.

GTP and Ca2+, two well-known modulators of intracellular signaling pathways, control a structural/functional switch between two vital and mutually exclusive activities, cross-linking and Galpha activity, in the same enzyme. The enzyme, a brain-derived tissue-type transglutaminase (TGase), was recently cloned by us in two forms, one of which (s-TGN) lacks a C-terminal region that is present in the other (l-TGN). Immunoreaction with antibodies directed against a peptide present in the C-terminus of l-TGN but missing in s-TGN suggested that this site, which is located in the C-terminal fourth domain, undergoes conformational changes as a result of interaction between l-TGN and GTP. Site-directed mutagenesis suggested that the third domain is involved in mediating the inhibition of the cross-linking activity. These results were supported by molecular modeling, which further suggested that domains III and IV both participate in conformational changes leading to the functional switch between the Ca2+-dependent cross-linking activity and the Galpha activity.

Expression of GTP-dependent and GTP-independent tissue-type transglutaminase in cytokine-treated rat brain astrocytes.

Tissue-type transglutaminases (TGases) were recently shown to exert dual enzymatic activities; they catalyze the posttranslational modification of proteins by transamidation, and they also act as guanosine triphosphatase (GTPase). Here we show that a tissue-type TGase is expressed in rat brain astrocytes in vitro, and is induced by the inflammation-associated cytokines interleukin-1beta and to a lesser extent by tumor necrosis factor-alpha. Induction is accompanied by overexpression and appearance of an additional shorter clone, which does not contain the long 3'-untranslated region and encodes for a novel TGase enzyme whose C terminus lacks a site that affects the enzyme's interaction with guanosine triphosphate (GTP). Expression of two clones revealed that the long form is inhibited noncompetitively by GTP, but the short form significantly less so. The different affinities for GTP may account for the difference in physiological function between these two enzymes.

Adrenalectomy decreases vasoactive intestinal peptide mRNA levels in the rat suprachiasmatic nucleus.

Vasoactive intestinal peptide (VIP) concentrations were shown to be regulated by adrenal steroids. Therefore, we investigated whether adrenal steroids affect VIP mRNA levels, which would suggest an effect on VIP mRNA expression. Adrenalectomy performed on adult male rats resulted in a significant decrease in VIP mRNA in the hypothalamus (from 10.6 +/- 0.3 to 3.5 +/- 0.2 arbitrary units). In situ hybridization experiments revealed that a major site of VIP mRNA expression in the hypothalamus is the suprachiasmatic nucleus. Indeed, adrenalectomy resulted in an approximate decrease by half in VIP transcripts in this nucleus. However, this decrease was not reversed by replacement treatment with corticosterone or the glucocorticoid agonist, RU28362. Thus, VIP mRNA may be regulated by indirect mechanisms, influenced by the adrenal gland.

Cloning and characteristics of fish glial fibrillary acidic protein: implications for optic nerve regeneration.

Mammalian central nervous system neurons do not regenerate after axonal injury, unlike their counterparts in fish and amphibians. After axonal injury, glial cells in mammals do not support regrowth of axons, while in fish they support the regeneration process. Controversy exists as to whether or not the intact fish optic nerve expresses glial fibrillary acidic protein, a well-known marker for mature astrocytes, and thus whether its astrocytes differ in this respect from those of the brain and spinal cord, as well as from optic nerve astrocytes of other species. In an attempt to resolve this question we cloned fish glial fibrillary acidic protein. Two different complementary DNA clones were isolated from a carp brain complementary DNA library, each encoding a different form of glial fibrillary acidic protein apparently originating from different genes. Monospecific polyclonal antibodies were raised against a peptide synthesized according to the predicted amino acid sequence, and used to identify and localize the fish glial fibrillary acidic protein. Two glial fibrillary acidic proteins (of 49 kDa and 51 kDa) were identified by the antibodies in all tested fish central nervous system tissues. The antibodies were then used to examine glial fibrillary acidic protein immunoreactivity in sections taken from uninjured and injured optic nerves of goldfish. Injury was followed by an elevation in glial fibrillary acidic protein immunoreactivity along the whole length of the nerve, except at the site of the injury, where--as in the case of vimentin--no immunoreactivity was detectable. However, in contrast to vimentin-positive glial cells, which repopulate the site of the injury soon after the optic nerve is injured, glial fibrillary acidic protein-positive glial cells remained outside the injury site for as long as 6 weeks after the injury. Despite the injury-induced changes in glial fibrillary acidic protein immunoreactivity, no change was observed in the level of transcript encoding glial fibrillary acidic protein after injury, while there was an increase in the amount of glial fibrillary acidic protein associated with the cytoskeleton and a reduction in the soluble form. These results suggest that the injury-induced changes in immunoreactivity on sections involve changes not in transcription or translation of glial fibrillary acidic protein, but in glial fibrillary acidic protein compartmentalization.

Isolation and sequence analysis of two intermediate filament cDNA clones from fish optic nerve.

The high post-traumatic regenerative ability of fish central nervous system has been partially attributed to the hospitable nature of the surrounding non-neuronal cells and their appropriate response to injury. Uncovering the correlation between fish non-neuronal cell structure and behavior might yield a better understanding of what makes them supportive to axonal growth. Towards this goal, structural proteins expressed by fish non-neuronal cells need to be characterized. In the present study we isolated cDNA clones encoding fish intermediate filaments which are prominent structural proteins in astrocytes. Among the isolated clones, one was identified as fish vimentin and another was found identical to the cloned fish keratin 8. Results are discussed with respect to the use of these cDNAs for further understanding of fish non-neuronal cell plasticity.

Glial fibrillary acidic protein in the fish optic nerve.

The intermediate filament glial fibrillary acidic protein (GFAP) is the predominant cytoskeletal protein of mature glial cells in the mammalian nervous system. The nervous systems of lower vertebrates, such as fish, have been examined for the presence of GFAP and several investigators have shown that goldfish (Carassius auratus) brain contains GFAP-positive astrocytes. The same studies have demonstrated that, in contrast to the brain, the optic nerve of goldfish did not show any GFAP immunoreactivity, suggesting that this intermediate filament protein is not expressed in fish optic nerve astrocytes. The present study shows, however, that the monoclonal antibodies to porcine GFAP react with the optic nerve of carp (Cyprinus carpio), another member of the goldfish family. These antibodies to porcine GFAP cross react with rat brain and carp optic nerve, yielding a band of approximately 52 kDa in both species. Northern blot analysis using mouse GFAP DNA probe revealed that carp optic nerve RNA contains two transcripts of 2.3 and 2.1 kb, which hybridize with the mouse GFAP probe. Injury to the carp optic nerve was followed by a decrease of GFAP immunoreactivity from neural tissue and a strong expression around blood vessels and connective tissues. On the basis of these observations and within the limitation of the techniques it is reasonable to conclude that the carp optic nerve expresses GFAP immunoreactivity and that the pattern of expression of this intermediate filament protein is altered after injury. Such an alteration might be relevant to the process of regeneration.

The complete structure of the rat VIP gene.

Vasoactive intestinal polypeptide (VIP) is a regulatory neuropeptide/neurotransmitter of 28 amino acids involved in a wide variety of physiological functions. Using synthetic oligodeoxynucleotide probes related to the rat VIP-cDNA, we have isolated and characterized the gene encoding the rat pre-pro VIP/PHI-27 and compared it to the human VIP gene. The rat VIP gene spanned 7400 base pairs, and contained 7 exons interrupted by 6 introns. 100% identity was found between the gene exons and the cDNA sequence. Differences in sizes of introns 2, 4 and 5 (shorter in the rat gene) are the reason for the shorter rat gene compared with the human gene of 8837 base pairs. Comparison of the genes in the two species showed a high homology in the exon sequences, 80-90% in exons 2, 4, 5, 6 and 30-50% in exons 1 and 7. In addition, the exon-intron junctions shared high identity between the genes. The rat untranslated exon 1 had little homology (30%) with human exon 1 and was 13 base pairs shorter. Interestingly, the 160 base pairs at the 5'-flanking region upstream of the cap-site share more than 75% identity between the two genes, including the exact position of TATA-boxes in positions -28, -145, -155, a cAMP-responsive element in position -80 and a CAAT sequence in position -127. The conservation of the 5'-flanking region of the VIP gene in parallel with the conservation of its coding exons emphasize the importance of these sequences during evolution.